Fructosamine-3-kinase explained
Fructosamine-3-kinase is an enzyme that in humans is encoded by the FN3K gene.[1] [2] [3]
Function
FN3K catalyzes phosphorylation of fructosamines formed by glycation, the nonenzymatic reaction of glucose with primary amines followed by Amadori rearrangement. Phosphorylation of fructosamines may initiate metabolism of the modified amine and result in deglycation of glycated proteins.[3] [4]
FN3K is responsible for the formation of fructose 3-phosphate (F3P), a compound identified in the lenses of diabetic rats. The spontaneous decomposition of F3P leads to the formation of 3-deoxyglucosone (3DG). 3DG contributes to diabetic complications. Treatment of normal and diabetic rats with an inhibitor of FN3K demonstrated a large reduction (~50%) in systemic 3DG in both groups. Removal of 3DG at its source by inhibition of FN3K is a viable option to treat diabetes related diseases since it would require a much smaller dose of drug.
Further reading
- Delpierre G, Rider MH, Collard F . Identification, cloning, and heterologous expression of a mammalian fructosamine-3-kinase. . Diabetes . 49 . 10 . 1627–34 . 2000 . 11016445 . 10.2337/diabetes.49.10.1627 . etal.
- Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .
- Ota T, Suzuki Y, Nishikawa T . Complete sequencing and characterization of 21,243 full-length human cDNAs. . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . etal. free .
- Delpierrre G, Vertommen D, Communi D . Identification of fructosamine residues deglycated by fructosamine-3-kinase in human hemoglobin. . J. Biol. Chem. . 279 . 26 . 27613–20 . 2004 . 15102834 . 10.1074/jbc.M402091200 . etal. free .
- Delplanque J, Delpierre G, Opperdoes FR, Van Schaftingen E . Tissue distribution and evolution of fructosamine 3-kinase and fructosamine 3-kinase-related protein. . J. Biol. Chem. . 279 . 45 . 46606–13 . 2004 . 15331600 . 10.1074/jbc.M407678200 . free .
- Conner JR, Beisswenger PJ, Szwergold BS . The expression of the genes for fructosamine-3-kinase and fructosamine-3-kinase-related protein appears to be constitutive and unaffected by environmental signals. . Biochem. Biophys. Res. Commun. . 323 . 3 . 932–6 . 2004 . 15381090 . 10.1016/j.bbrc.2004.08.181 .
- Gerhard DS, Wagner L, Feingold EA . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . etal.
- Conner JR, Beisswenger PJ, Szwergold BS . Some clues as to the regulation, expression, function, and distribution of fructosamine-3-kinase and fructosamine-3-kinase-related protein. . Ann. N. Y. Acad. Sci. . 1043 . 824–36 . 2005 . 1 . 16037310 . 10.1196/annals.1333.095 . 2005NYASA1043..824C . 19916880 .
- Delpierre G, Veiga-da-Cunha M, Vertommen D . Variability in erythrocyte fructosamine 3-kinase activity in humans correlates with polymorphisms in the FN3K gene and impacts on haemoglobin glycation at specific sites. . Diabetes Metab. . 32 . 1 . 31–9 . 2006 . 16523184 . 10.1016/S1262-3636(07)70244-6 . etal.
See also
Notes and References
- Szwergold BS, Howell S, Beisswenger PJ . Human fructosamine-3-kinase: purification, sequencing, substrate specificity, and evidence of activity in vivo . Diabetes . 50 . 9 . 2139–47 . Aug 2001 . 11522682 . 10.2337/diabetes.50.9.2139 . free .
- Delpierre G, Van Schaftingen E . Fructosamine 3-kinase, an enzyme involved in protein deglycation . Biochem Soc Trans . 31 . Pt 6 . 1354–7 . Dec 2003 . 14641062 . 10.1042/BST0311354 .
- Web site: Entrez Gene: FN3K fructosamine 3 kinase.
- Delpierre G, Collard F, Fortpied J, Van Schaftingen E . Fructosamine 3-kinase is involved in an intracellular deglycation pathway in human erythrocytes . Biochem. J. . 365 . Pt 3 . 801–8 . August 2002 . 11975663 . 1222720 . 10.1042/BJ20020325 .
